The invention relates to the fields of organic synthesis, medicinal chemistry, cancer chemotherapeutic agents and cancer chemotherapy. Specifically, the invention relates to microtubule-stabilizing antitumor compounds of the epothilone class.
Epothilones are macrolide compounds which find utility in the pharmaceutical field. For example, Epothilones A and B having the structures: 
have been found to exert microtubule-stabilizing effects similar to TAXOL(trademark) and hence cytotoxic activity against rapidly proliferating cells, such as, tumor cells or other hyperproliferative cellular disease; see Hofle et al., Angew. Chem. Int. Ed. Engl., 1996, 35:1567-1569.
The present invention relates to compounds of formula I and formula II: 
Q is selected from the group consisting of 
G is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, 
L is O, S, SO, SO2 or NR13 or CR14R15;
W is O or NR16;
X is O, S, CHR17 or H, R18;
Z is O; S; H, R19 or R20, R21;
Y is selected from the group consisting of O; H, H; H, OR22; OR23, OR23; NOR24; H, NOR25; H, NR26R27; NHNR28R29; H, NHNR30R31; or CHR32; where OR23, OR23 can be a cyclic ketal;
B1 and B2 are selected from the group consisting of H, OR33, OCOR34, OCONR35R36, NR37R38 or NR39CONR40R41;
D is selected from the group consisting of NR42R43 or heterocyclo;
M is selected from the group consisting of S, Cxe2x95x90O, Sxe2x95x90O, SO2, NR44, or CR45R46;
J, E, U, and V are selected from carbon, oxygen, nitrogen or sulfur; or V may be absent;
R1, R2, R3, and R4, are selected from H, lower alkyl;
R5, R8, R9, R10 and R11 are selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, heterocyclo or substituted heterocyclo;
R6 and R7 are selected from the group consisting of H, alkyl, substituted alkyl, halogen, nitro, cyano, OR47, NR48R49, R50Cxe2x95x90O;
R17, R18, R22 and R23 are selected from the group consisting of H, alkyl, and substituted alkyl;
R20, R21, R24, R25, R26, R28, R30, R32, R33, R34, R35, R36, R37, R39, R40, R41, R42, R47, R48, R50, R52, R53, R54, R56, R57, R58, R59, R61, R62, R64, and R65 are selected from the group of H, alkyl, substituted alkyl, aryl, substituted aryl; heterocyclo or substituted heterocyclo;
R63 is H, alkyl having 2 to 20 carbon atoms, substituted alkyl, aryl, substituted aryl; heterocyclo or substituted heterocyclo;
or R62 and R63, together with the nitrogen atom to which they are attached, form a heterocycle or substituted heterocycle;
R51 is heterocyclo or substituted heterocyclo;
R12, R13, R16, R27, R29, R31, R38, R43, R49, R55 and R60 are selected from the group consisting of H, alkyl, substituted alkyl, substituted aryl, cycloalkyl, heterocyclo, R51Cxe2x95x90O, R52OCxe2x95x90O, R53SO2, hydroxy, O-alkyl or O-substituted alkyl; when X is O then R16 is not R51Cxe2x95x90O, R52OCxe2x95x90O, and R53SO2; and wherein R44 is further amino and R61R64NCxe2x95x90O;
R44 is R51Cxe2x95x90O, R62R63NSO2, or (Cxe2x95x90O)xe2x80x94(Cxe2x95x90O)xe2x80x94R65;
R14 and R15 are selected from the group consisting of H, halogen, alkyl, or substituted alkyl;
R19 is selected from the group consisting of H, alkyl, substituted alkyl, O-alkyl, O-substituted alkyl, NR54R55, R56Cxe2x95x90O; when L is O, S, or NR13 then R19 is not O-alkyl, O-substituted alkyl, NR54R55.
R45 and R46 are selected from the group consisting of H, halogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, heterocyclo, R56Cxe2x95x90O, R57OCxe2x95x90O, R58NHCxe2x95x90O, hydroxy, O-alkyl or O-substituted alkyl, NR59R60;
and any salts, solvates or hydrates thereof, with the proviso that
when Q is 
M is CR45R46 then W is only NR16.